The invention relates to methods for fabricating inorganic membrane devices, and more particularly to methods for fabricating inorganic membrane devices for separating biomolecules.
Typically, membrane filters are employed in biological applications involving separation of molecules in biological fluids. Most of the membrane filters employ polymer membranes or ceramic membranes. For example, cellulose and its derivatives, polysulfone, polyacrylonitride (PAN), poly(methylmethacrylate) (PMMA), polyamide, polypropylene, polycarbonatem, polyester, polyvinylidene fluoride, anodic aluminum oxide are some of the materials used to make membranes. Disadvantageously, most of the existing membranes have broad pore size distribution. In other words, the sizes of the pores in a given membrane are inconsistent and vary greatly over a large range. Due to large pore size distribution, the separation process suffers significant product loss. For example, species pass through the filter due to large pore size distribution when they should be retained. Another disadvantage is that these membranes are quite thick and, as a result, have relatively low flux rates, thereby adversely affecting the throughput of the filtration process. These ceramic membranes also typically lack the robustness needed to scale up for protein and other biomolecule processing.
Some demanding filtration applications, for example virus filtration or clearance, require very small pore sizes (15 nanometers to 35 nanometers) and high flux rate. The membrane needs to have very narrow pore distribution to achieve greater than 5 logs virus reduction. The filtration layer of the membrane also needs to be very thin to achieve high flux rates because the filtration resistance can be very high for a pore size in a range from about 15 nanometers to about 35 nanometers. The ultrathin inorganic membranes, such as silicon or silicon nitride membranes, have very narrow pore size distribution in a broad range of nanopores from 5 nanometers to greater than 1 micrometer, and very thin membrane layers from 10 nanometers to greater than about 1 micrometers.
Therefore, it would be desirable to provide a method for making a membrane that has uniform pore size distribution and enhanced robustness for use in virus filtration.